Treatment of Hydroxychloroquine in Type 2 Diabetes Patients Uncontrolled on Metformin Monotherapy
Scientific Title of Study
Evaluation of Efficacy and Safety of Hydroxychloroquine when Used as an Add-on Therapy in Type 2 Diabetes Patients Uncontrolled on Metformin Monotherapy: A Randomized Double-blind, Placebo-controlled Study
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
Ipca/HCQP/PIII-20 08022021 V2 Amendment1
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Anil Pareek
Designation
President
Affiliation
Ipca Laboratories Ltd.
Address
Medical Affairs and Clinical Research department, Plot 142-AB, 2d floor
Kandivli Industrial Estate, Kandivli (West) Mumbai (Suburban) MAHARASHTRA 400067 India
Phone
02266474641
Fax
Email
anil.pareek@ipca.com
Details of Contact Person Scientific Query
Name
Dr Anil Pareek
Designation
President
Affiliation
Ipca Laboratories Ltd.
Address
Medical Affairs and Clinical Research department, Plot 142-AB, 2nd floor
Kandivli Industrial Estate, Kandivli (West) Mumbai (Suburban) MAHARASHTRA 400067 India
Phone
02266474641
Fax
Email
anil.pareek@ipca.com
Details of Contact Person Public Query
Name
Nitin Chandurkar
Designation
Vice President
Affiliation
Ipca Laboratories Ltd.
Address
Medical Affairs and clinical research department, Clinical Research and Development division, Plot 142-AB, 2nd floor,
Kandivli Industrial Estate, Kandivli (West) Mumbai (Suburban) MAHARASHTRA 400067 India
Department of Medicine, Calicut Medical College and Hospital, Medical College Road, Government Medical College Campus, Kozhikode, Calicut- 673008 Kozhikode KERALA
9447391055
nmanikath@gmail.com
Dr Nihal Thomas
Christian Medical College
Christian Medical College, 810, Department of Endocrinology Diabetes & Metabolism, Christian Medical College, Vellore-632004
Vellore TAMIL NADU
9843111996
nihal_thomas@yahoo.com
Dr Madhuri Kirloskar
Dr. Vasantrao Pawar Medical College, Hospital & Research Centre
Dr. Vasantrao Pawar Medical College, Hospital & Research Centre, Vasantdada Nagar, Adgaon, Nashik, 422003 Nashik MAHARASHTRA
9822018284
mskirloskar@gmail.com
Dr Richa Giri
Ganesh Shankar Vidyarthi Memorial Medical College
Department of Medicine, Ganesh Shankar Vidyarthi Memorial Medical College, Swaroop Nagar, Kanpur- 208002 Kanpur Nagar UTTAR PRADESH
8400331045
drrichagiri.gsvm@gmail.com
Dr Parul Bhatt
GMERS Medical College and Hospital
Department of Medicine, GMERS Medical College and Hospital, Sola, Nr. Gujarat High Court, S. G. Highway, Sola, Ahmedabad-380060 Ahmadabad GUJARAT
9879599595
parulbhatt30@yahoo.com
Dr Vishwajeet Gaikwad
Imperial Multispeciality Hospital
Imperial Multispeciality Hospital, Pingle Pride, Nr. Radha Swami Ashram, Chikhali, Pune-411062. Pune MAHARASHTRA
9430475068
dr.vishwajeetgaikwad@gmail.com
Dr Madhumati Varma
Jaipur National University
JNUIMRC, Near New RTO office, Jaipur-Agra road, Jagatpura, Jaipur-302017 Jaipur RAJASTHAN
KIMS Hospital, Department of General Medicine, B block, Ground Floor, KR road, V V Puram, Banglore 560004 Bangalore KARNATAKA
9535410888
drnagesh10@yahoo.com
Dr Ramanathan Balamurugan
Kovai Diabetes Speciality Centre & Hospital
Kovai Diabetes Speciality Centre & Hospital, 15, Vivekananda Road, Ram Nagar, Coimbatore- 641009 Coimbatore TAMIL NADU
9842244881
rbmkdsc@gmail.com
Dr L Sreenivasa Murthy
Life Care Hospital & Research Center
Life Care Hospital & Research Center, #2748/2152 M.L.N. Enclave, 16th E-Cross road, 8th Main D Block, Next to Corporation Bank, Sahakarnagar, Bengaluru-560092 Bangalore KARNATAKA
8023631055
drlsm@lcrc.in
Dr Amol Dange
Lifepoint Multispeciality Hospital
Lifepoint Multispeciality Hospital, 145/1, Mumbai Bangalore Highway, Near Hotel Sayaji, Wakad, Pune- 411057 Pune MAHARASHTRA
9823912040
amoldange298@gmail.com
Dr Vijay Viswanathan
M. V. Hospital for Diabetes (P) Ltd
M. V. Hospital for Diabetes (P) Ltd., #4, West Madha Church Street, Royapuram, Chennai- 600013 Chennai TAMIL NADU
9840055535
drvijay@mvdiabetes.com
Dr Dinesh Agrawal
Marwari Hospitals
S J Road Athgaon Guwahati 781008 Assam Kamrup ASSAM
9864061456
drdinesh944@gmail.com
Dr Manish Agarwal
Medilink Hospital Research Center
Medilink Hospital Research Center, Near Shyamal Cross Road, 132ft. Ring Road, Satellite, Ahmedabad- 380015 Ahmadabad GUJARAT
9825443397
medilinkresearchcentre@yahoo.com
Dr Atul Rajkondwar
Meditrina Institute of Medical sciences
Meditrina Institute of Medical sciences, 7th floor research department, 278, central bazar road, Ramdaspeth, Nagpur-440010 Nagpur MAHARASHTRA
9373215775
atul.rajkondawar@gmail.com
Dr Kishor M Shelgikar
MMFHA Joshi Hospital
778 SHIVAJINAGAR OPPOSITE KAMALA NEHRU PARK PUN Pune MAHARASHTRA
9231674135
kmshelgikar@gmail.com
Dr Mukund Penurkar
MTES Sanjeevan Hospital
MTES Sanjeevan Hospital, Plot No. 23, Off Karve Road, Erandwane, Pune-411004 Pune MAHARASHTRA
02067250000 02067250015 drpenurkarm@gmail.com
Dr Krishnamurthy HA
Mysore Medical College and Research Institute
Department of General Medicine, Mysore Medical College and Research Institute, K. R. Hospital, Mysore- 570001 Mysore KARNATAKA
9880668121
kmha79@gmail.com
Dr Ashu Rastogi
Post Graduate Institute of Medical Education and Research
Department of Endocrinology & Metabolism, Post Graduate Institute of Medical Education and Research, Room no- 16, Ground floor, Nehru Extension Block, Chandigarh- 160012 Chandigarh CHANDIGARH
9781001046
ashuendo@gmail.com
Dr C L Nawal
S.M.S Medical College and Hospital
Department of Medicine, Ground floor, G-1, Dhanvantri OPD Block, S.M.S Medical College and Hospital, Jaipur- 302004 Jaipur RAJASTHAN
9414053160
drclnawal@gmail.com
Dr Indira Pattnaik
Sparsh Hospital and Critical Care (P) Ltd
Department of Medicine, Sparsh Hospital and Critical Care (P) Ltd, A-407, Saheed Nagar, Bhubaneswar-751007 Khordha ORISSA
9437246066
indirapattnaik8@gmail.com
Dr Sujit Chandratreya
Vijan Hospital & Research Centre
Vijan Hospital & Research Centre, College Road, Nashik- 422005 Nashik MAHARASHTRA
Institutional Ethics Committee, Dr. Vasantrao Pawar Medical College, Hospital & Research Centre, Nashik
Approved
Institutional Ethics Committee, JNU, Jaipur
Approved
Institutional Ethics Committee, JNU, Jaipur.
Approved
INSTITUTIONAL ETHICS COMMITTEE, K.I.M.S BANGLORE
Approved
Institutional Human Ethics Committe AIIMS Jodhpur
Approved
Institutional Review Board Christian Medical College Vellore
Approved
Life Care Hospital Institutional Review Board Bangalore
Approved
LPR Ehics Committee Lifepoint Multispeciality Hospital Pvt. Ltd. Pune
Approved
MAHARASHTRA MEDICAL RESEARCH SOCIETY
Approved
MAHE Ethics Committee Manipal Academy of Higher Education, Udupi
Approved
Medilink Ethics Committee Ahmadabad
Approved
Medisys Clinisearch Ethical Review Board Bangalore Diabetes Center Bangalore
Approved
MEDITRINA INSTITUTE ETHICS COMMITTEE
Approved
MTESs Ethics Committee Sanjeevan Hospital, Pune
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Hydroxychloroquine
Hydroxychloroquine 200 mg, 300 mg and 400 mg
administered once daliy for 24 weeks with existing
dose of metformin
Comparator Agent
Placebo
Matching placebo of HCQ 200 mg, 300 mg and 400 mg administered once daliy for 24 weeks with existing dose of metformin
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Patients diagnosed with T2D who are receiving stable dose of metformin (≥1000 mg/day) for at least 12 weeks
2. Patients with HbA1c between 7.0 % and 10 % (Both inclusive)
3. Patients with FPG >125 mg/dL and/or PPG ≥200 mg/dL
4. Patients with body weight ≥60 kg
5. Patients able to understand and willing to fully comply with study procedures and restrictions
6. Patient ready to give informed consent to participate in the study
ExclusionCriteria
Details
1. Patients with uncontrolled hyperglycemia i.e. FBG >240 mg/dL
2. Patients with Type 1 diabetes
3. Patients with endocrine disorders other than Type 2 diabetes mellitus
4. Patients with a history or presence of any retinopathy of any grade including diabetic retinopathy, evidence of an imminent need for laser therapy, uncorrected visual acuity <20/100, abnormal visual fields, difficulty to examine optic disc, or evidence of retinal pigment epithelial abnormalities and patients with history or risk of macular edema
5. Patients with QT prolongation (≥450 ms), ventricular arrhythmia or torsades de pointes
6. Patients with cardiovascular events i.e. myocardial infarction/acute coronary syndrome, stroke or has undergone coronary artery bypass surgery, percutaneous transluminal coronary angioplasty or transient ischemic attack, or history of congestive heart failure, cardiomyopathy or unstable angina in past
7. Patients with abnormal renal function (serum creatinine ≥1.5 mg/dL for male and ≥1.4 mg/dL for female)
8. Patients with abnormal liver function (SGOT, SGPT, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of normal values) or active or chronic liver disease or patients with CPK >2.5 times the upper limit of normal value
9. Patients with significantly abnormal counts in hematology, diseases of blood or hematopoietic organs or female patients with Hb <10 g/dL or male patients with Hb <12 g/dL
10. Patients with triglycerides ≥ 500 mg/dL
11. Patients with history of G6PD deficiency, aplastic anemia or agranulocytosis, granulocytopenia
12. Patients with history of psoriasis, blisters, porphyria, rash, scaling, scaling eczema
13. Patients with history of myalgia, proximal myopathy, neuropathy including symptomatic autonomic neuropathy
14. Patients with hs-CRP ≥10 mg/L
15. Patients with systolic BP >180 mmHg and/or diastolic BP >100 mmHg
16. Patients with chronic gastroparesis, active gastrointestinal disorders (gastric and duodenal ulcer)
17. Patients with known history of diabetic ketoacidosis
18. Patients with history of hypoglycemia unawareness (Patients whose blood glucose levels fall below 70 mg/dL but they do not feel any symptoms of hypoglycemia)
19. Patients with malignancy and planned radiological examinations requiring administration of contrasting agents
20. Patients with malabsorption or pancreatitis
21. Patients with dementia or other cognitive impairment prohibiting informed consent
22. Patients with known history of HIV1/HIV2/Hepatitis B or C infection or syphilis infection
23. Patient with any other illness for which HCQ is indicated (such as rheumatoid arthritis [RA], systemic lupus erythematosus [SLE] etc.)
24. Patients with any other clinically significant abnormalities/disease which may or may not interfere with assessment of disease under evaluation
25. Patients receiving/requiring insulin
26. Patients receiving other OHA
27. Patients receiving anti-obesity drugs or undergoing bariatric surgery within 24 weeks prior to consent
28. Patients receiving systemic steroids at the time of consent or have received it in past 3 months
29. Patients with chronic use of non-steroidal anti inflammatory agents
30. Patients receiving concomitant medications known to have an interaction with HCQ
31. Patients receiving drugs known to cause QT prolongation
32. Patients with known history of hypersensitivity to HCQ or other similar drugs of same chemical class or any other ingredient of the study formulations or with history of any severe allergic disease
33. Patients with substance abuse within the last year
34. Patients consuming alcohol more than 21 units /week
35. Patients on another investigational agent / device or participated in a clinical trial within the last 30 days prior to enrolment.
36. Pregnant or lactating women
37. Women of childbearing potential not practicing contraception
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate and compare mean change in glycated hemoglobin (HbA1c) between HCQ group and placebo group
At Week 24 from baseline
Secondary Outcome
Outcome
TimePoints
To evaluate and compare mean change in HbA1c between HCQ group and placebo group
At Week 12 from baseline
To evaluate and compare mean change in fasting blood glucose (FBG) and 2-h post-prandial blood glucose (PPG) between HCQ group and placebo group
At Week 12 and Week 24 from baseline
To evaluate and compare mean change in HbA1c, FBG, and PPG between different treatment groups
At Week 12 and Week 24 from baseline
To evaluate and compare percentage of patient achieving HbA1c level less than 7.0 percent between treatment groups
At Week 24
To assess safety and tolerability of study medications based on incidence of adverse events AEs clinical and laboratory, changes in laboratory parameters and incidences of hypoglycemia.
Throughout the duration of study
To evaluate and compare mean change in following parameters
Total Cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non HDL-C
Body weight, BMI, waist circumference and waist to hip ratio
High-sensitivity C-reactive protein (hs-CRP), white blood cells (WBC) and erythrocyte sedimentation rate (ESR)
At Week 12 and Week 24 from baseline
Target Sample Size
Total Sample Size="364" Sample Size from India="364" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="381"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a multicentric, randomized, placebo-controlled, double-blind, parallel-group study. A total of 364 patients with type 2 diabetes receiving a stable dose of metformin monotherapy at least 1000 mg/day for at least 12 weeks, weighing ≥ 60 kg, and satisfying the study inclusion/exclusion criteria will be randomized in 1:1:1:1 ratio to receive one of the following treatments for 24 weeks along with an existing dose of metformin (at least 1000 mg/day):
HCQ 200 mg + matching placebo of HCQ 300 mg + matching placebo of HCQ 400 mg
HCQ 300 mg + matching placebo of HCQ 200 mg + matching placebo of HCQ 400 mg
HCQ 400 mg + matching placebo of HCQ 200 mg + matching placebo of HCQ 300 mg
Matching placebo of HCQ 200 mg + matching placebo of HCQ 300 mg + matching placebo of HCQ 400 mg